Department of Hematology and Oncology, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Taizhou, Zhejiang, China (mainland).
Med Sci Monit. 2019 Jul 13;25:5211-5218. doi: 10.12659/MSM.915840.
BACKGROUND T cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy caused by abnormal proliferation of immature T cell progenitors. Chemotherapy of T-ALL usually consists of induction, consolidation, and long-term maintenance. Diacetyl hexamethylene diamine (CAHB) is a newly developed agent that induces the differentiation of malignant cells and deprives their clonal growth ability. Since its effect on T-ALL has not been previously determined, we evaluated its potential function in the Jurkat cell line. MATERIAL AND METHODS MTT assay was conducted to evaluate the cytotoxicity and anti-proliferative effect of CAHB. The apoptosis level of CAHB-treated Jurkat cells was evaluated using flow cytometry via staining with Annexin V/PI or cleaved-caspase-3. The alteration of mitochondrial membrane potential was determined by flow cytometry. The expression of Bax and Bcl-2 was evaluated by RT-PCR and Western blot. Western blot was also used to assess the activation of Akt. RESULTS CAHB inhibited the proliferation and promoted the apoptosis of Jurkat cells in a time- and dose-dependent manner by decreasing activation of Akt, reducing the mitochondrial membrane potential, and downregulating the Bcl-2/Bax ratio. CONCLUSIONS Our data suggest that CAHB might be regarded as a novel treatment agent for T-ALL since it can induce apoptosis and inhibit proliferation of the T-ALL cell line at a relatively low level.
T 细胞急性淋巴细胞白血病（T-ALL）是一种由不成熟 T 细胞前体异常增殖引起的侵袭性血液系统恶性肿瘤。T-ALL 的化疗通常包括诱导、巩固和长期维持。己二酰六亚甲基二胺（CAHB）是一种新开发的药物，可诱导恶性细胞分化并剥夺其克隆生长能力。由于其对 T-ALL 的作用尚未确定，我们评估了其在 Jurkat 细胞系中的潜在功能。
MTT 法评估 CAHB 的细胞毒性和抗增殖作用。用 Annexin V/PI 或 cleaved-caspase-3 染色通过流式细胞术评估 CAHB 处理的 Jurkat 细胞的凋亡水平。通过流式细胞术测定线粒体膜电位的变化。通过 RT-PCR 和 Western blot 评估 Bax 和 Bcl-2 的表达。Western blot 还用于评估 Akt 的激活。
CAHB 通过降低 Akt 的激活、减少线粒体膜电位和下调 Bcl-2/Bax 比值，以时间和剂量依赖的方式抑制 Jurkat 细胞的增殖并促进其凋亡。
我们的数据表明，CAHB 可能被视为 T-ALL 的一种新型治疗剂，因为它可以在相对较低的水平诱导 T-ALL 细胞系的凋亡和抑制增殖。
